PubMed · 2392147
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P H Duesberg. 1990-08-30. Duesberg replies.. https://doi.org/10.1038/346788b0
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Although developments in small-molecule therapeutics for HIV-1 have been dramatic in recent years, the rapid selection of drug-resistant viral strains and the adverse side effects associated with long-term exposure to current treatments propel continued exploration of alternative anti-HIV-1 agents. Non-coding nucleic acids have emerged as potent inhibitors that dramatically suppress viral function both in vitro and in cell culture. In particular, RNA and DNA aptamers inhibit HIV-1 function by directly interfering with essential proteins at critical stages in the viral replication cycle (Figure 1). Their antiviral efficacy is expected to be a function, in part, of the biochemical properties of the aptamer-target interaction. Accordingly, we present an overview of biochemical and cell culture analyses of the expanding list of aptamers targeting HIV-1. Our discussion focuses on the inhibition of viral enzymes (reverse transcription, proteolytic processing, and chromosomal integration), viral expression (Rev/RRE and Tat/TAR), viral packaging (p55Gag, matrix and nucleocapsid), and viral entry (gp120) (Table 1). Additional nucleic acid-based strategies for inactivation of HIV-1 function (including RNAi, antisense, and ribozymes) have also demonstrated their utility. These approaches are reviewed in other chapters of this volume and elsewhere.
Despite significant progress over the last two decades, treatment of HIV infection remains a tremendous challenge. Although antiretroviral therapy has proved quite effective in most HIV-infected patients, increasing recognition of toxicity and the emergence of multidrug resistant HIV strains has fueled the development of alternative therapeutic approaches. Introduction of genes to inhibit HIV replication into CD4+ T lymphocytes or hematopoietic stem cells represents a potentially attractive but still unproven strategy. Despite the availability of a diverse range of molecular strategies that are able to provide potent inhibition of HIV replication in the laboratory, translation of these in vitro successes to in vivo therapies has been difficult. Fundamental challenges facing AIDS gene therapy at the present time includes the need to increase the efficiency of gene transfer in vivo, to confer upon genetically-modified T cells the ability to have a selective growth advantage in vivo, and the development of additional techniques to decrease the probability of emergence of resistant viruses. As one of the leading animal models for AIDS and for hematopoietic stem cell gene therapy, nonhuman primates are ideally suited to help address many of these basic questions. This review will provide a general overview of RNA-based genetic strategies for inhibition of HIV and SIV replication, criteria to be considered in the selection of promising inhibitory strategies for in vivo use, and key questions that can be addressed in the macaque model.
Sources of AIDS awareness among rural and urban Indian women were analysed using data from the National Family and Health Survey (1998-2000). Two measures were developed to study the impact each source had on knowledge. 'Effectiveness' was defined as the proportion of women who had heard of AIDS from only one source, from among women who had heard of AIDS from that particular source and other sources. 'Independent effect' was the proportion who had heard of AIDS from only one source in relation to all women who had heard of AIDS. Television was the most effective medium, and also had the highest independent effect. Radio and print had very low effectiveness and independent effect. Although television and print audiences are growing in India, it is likely a sub-group of women will continue to lack media access. There is an urgent need to disseminate AIDS awareness to this 'media underclass'. Since the media will not reach this group, other sources including health workers, community level activities such as adult education programmes, and networks of friends and relatives need to be explored.